The proposed investigations on Hageman factor (human coagulation Factor XII) and on the Hageman factor pathways are designed to provide fundamental biochemical and physicochemical knowledge about the activation and control of the components of the Hageman factor pathways. These pathways include: the intrinsic clotting system, the kallikrein-kinin system, and the plasmin-fibrinolytic system. Detailed knowledge about the molecular mechanisms of activation and enzymatic specificity of Hageman factor and its substrate proteins (kallikrein, Factor XI, and plasminogen proactivator) is essential to the long-range goal of a thorough evaluation of the contributions of the Hageman factor pathways to the pathogenesis of disease.